title: Structure-function alteration of hemoglobin in arsenicosis patients: a probable pathway to exert toxicity.
abstract: Chronic arsenicosis, a major public health concern in India and Bangladesh, is mainly caused by ingestion of arsenic (As) contaminated ground water. Although this problem has been studied extensively, the mechanism of toxicity remains unknown. This paper investigates the process of trivalent arsenicals binding to hemoglobin (Hb) in chronic arsenicosis patients and consequent modification in the structure-function activity of Hb. In this work peroxidase activity, thermal denaturation profile, oxygen releasing capacity and hydrodynamic diameter have been evaluated for the Hb collected from subjects suffering with chronic arsenicosis. Increased peroxidative activity suggests altered oxidative status of Hb in the diseased state. The thermal denaturation profile indicates the Hb molecule to be more susceptible to unfolding in the pathologic state. The enhanced oxygen releasing capacity and significant reduction in hydrodynamic diameter of Hb is also observed in the diseased condition, suggesting conformational alterations in the Hb molecule. Finally, trivalent arsenic is found to bind with freshly isolated Hb from arsenicosis patients, binding affinity constant being 0.256 μM⁻¹. The binding is positively cooperative with a Hill coefficient of +2.961 and isosbestic points at specific wavelengths. Thus, our work explores the structure-function property of Hb in chronic arsenicosis subjects and reveals that the molecule is modified in such a way that comparatively weak binding with oxygen and strong binding with arsenic occur simultaneously. This association may play a crucial role in exerting the pathway for arsenic toxicity.
authors.affiliation: Department of Biochemistry, University of Calcutta, 35 Ballygunge Circular Road, Kolkata 700019, India.
authors.forename: Bibaswan
authors.initials: B
authors.lastname: Mondal
authors.forename: Debdutta
authors.initials: D
authors.lastname: Chatterjee
authors.forename: Maitree
authors.initials: M
authors.lastname: Bhattacharyya
mesh_terms: D000328:Adult; D001151:Arsenic / Q000633:toxicity*; D020261:Arsenic Poisoning / Q000097:blood*; D001459:Bangladesh; D004198:Disease Susceptibility; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D006454:Hemoglobins / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D013329:Structure-Activity Relationship; D014874:Water Pollutants, Chemical / Q000032:analysis
chemical_list: D006454:Hemoglobins; D014874:Water Pollutants, Chemical; D001151:Arsenic